Skeletal Muscle Sympathetic Nerve Activity Research Articles

Glucocorticoid-induced sympathoinhibition in humans

To test whether glucocorticoids inhibit sympathetic nerve activity or norepinephrine release in humans, as has been suggested by results in laboratory animals. This was a double-blind, placebo-controlled, randomized crossover study performed at the Clinical Center of the National Institutes of Health. Thirteen normal volunteers received 20 mg prednisone or placebo orally each morning for 1 week, followed by a washout period of 1 week and then by treatment with the other drug for 1 week. On the last day of each treatment week, blood samples were drawn for measurements of plasma levels of catecholamines and their metabolites, of cortisol, and of corticotropin at baseline and during reflexive sympathetic stimulation elicited by lower body negative pressure (-15 mm Hg). A 24-hour urine collection was obtained at the end of each week of treatment for measurement of urinary excretion of catechols. In eight subjects, directly recorded peroneal skeletal muscle sympathetic nerve activity was also measured after both treatments. Prednisone significantly decreased sympathetic nerve activity by 23% +/- 6%, plasma norepinephrine levels by 27% +/- 6%, and plasma corticotropin levels by 77%. Blood pressure, heart rate, body weight, and urinary excretion of catechols and electrolytes were unaffected. Prednisone did not alter proportionate increments in sympathetic nerve activity or plasma norepinephrine levels during lower body negative pressure. Relationships between sympathetic nerve activity and plasma norepinephrine levels were unchanged. Glucocorticoids decrease sympathoneural outflows in humans without affecting acute sympathoneural responses to decreased cardiac filling and probably without affecting presynaptic modulation of norepinephrine release.

Glucocorticoids, sympathetic activity, and presynaptic alpha 2-adrenoceptor function in humans.

The sympathetic nervous system and the pituitary-adrenocortical system are two of the body's main stress effector systems. Animal studies have indicated that exogenously administered glucocorticoids inhibit sympathetic outflows and interfere with the function of presynaptic alpha 2-adrenoceptors modulating neuronal norepinephrine (NE) release. The present study tested whether glucocorticoids produce similar effects in humans. In a randomized, double-blind, placebo-controlled cross-over experiment, 15 healthy subjects took 20 mg prednisone or placebo orally daily each morning for 1 week, followed by the other drug after a 1-week washout. On the last day of each treatment week, blood samples were drawn for assays of plasma levels of catechols and ACTH before and after iv infusion of the alpha 2-adrenoceptor antagonist yohimbine (YOH) (0.125 mg/kg bolus, 0.001 mg.kg-1.min-1 infusion). In 7 subjects, directly recorded peroneal skeletal muscle sympathetic nerve activity (MSNA) was also measured at baseline and after YOH infusion at the end of both treatment weeks. Prednisone decreased plasma NE levels and MSNA compared with levels after placebo (1.09 +/- 0.11 nmol/L vs. 1.40 +/- 0.13 nmol/L, P < 0.01; 30 +/- 4 bursts/min vs. 36 +/- 3 bursts/min, P < 0.05) without affecting blood pressure or pulse rate. YOH increased mean arterial blood pressure by 12% (P < 0.001) and heart rate by 7% (P < 0.05); prednisone did not alter these effects of YOH. YOH-induced proportionate increments in plasma NE levels averaged about 10 times those in MSNA. Prednisone did not affect the YOH-induced proportionate increments in plasma NE levels (placebo, 243%; prednisone, 237%) or MSNA (placebo, 22%; prednisone, 23%). The decrements in MSNA and plasma NE levels after prednisone treatment indicate that glucocorticoids inhibit sympathoneural outflows in humans. The 10-fold larger NE than MSNA response to YOH confirms substantial inhibitory modulation of NE release by alpha 2-adrenoceptors on noradrenergic terminals, and the similarity of responses to YOH after prednisone or placebo suggests that glucocorticoid-induced sympathoinhibition occurs independently of altered modulatory function of alpha 2-adrenoceptors on noradrenergic terminals.

Respiratory modulation of muscle sympathetic nerve activity in intact and lung denervated humans.

We determined the influences of breathing-induced changes in intrathoracic and intravascular pressures, central respiratory drive, and pulmonary vagal feedback on the within-breath variation in skeletal muscle sympathetic nerve activity (MSNA) in humans. MSNA (peroneal microneurography), arterial blood pressure (Finapres finger monitor), and tidal volume (VT) were recorded continuously in six normal subjects and four heart-lung transplant patients during: 1) spontaneous air breathing; 2) increased FICO2; 3) voluntary augmentation of VT with and without inspiratory resistance; and 4) positive pressure, passive mechanical ventilation. During conditions 3 and 4, which were performed under isocapnic conditions with a high MSNA background (either high resting activity or nonhypotensive lower body suction), subjects breathed at control or elevated VT with normal or prolonged inspiratory time (TI); breathing frequency was 12 breaths per minute. During control breathing in normal subjects there was a distinct within-breath pattern of MSNA, with approximately 70% of the activity occurring during low lung volumes (initial half of inspiration and latter half of expiration). This within-breath variation of MSNA was potentiated with increased VT breathing (> 85% of activity occurring during low lung volumes; p < 0.05 versus control breathing) and was similar during the voluntary and CO2-induced hyperpneas. MSNA decreased progressively and markedly from onset to late inspiration; fell slightly further, reaching its nadir at end-inspiration/onset-expiration; and rose sharply during mid-late expiration. Only the nadir of MSNA was associated with any change in arterial pressure. Resistive breathing, especially at elevated VT, caused a fall in arterial pressure and increased respiratory drive during inspiration, yet MSNA still declined as lung volume increased. Normal within-breath modulation of MSNA also was observed during control and elevated VT induced via positive pressure with passive ventilation, which reversed lung inflation/deflation-induced intrathoracic pressure changes and reduced or removed respiratory motor output. During control breathing in transplant patients the specific within-breath pattern of MSNA was somewhat different than that of the normal subjects, but on average, the overall low lung volume to high lung volume MSNA ratio was similar to normal subjects. In contrast to the normal subjects, however, there was no potentiation of the within-breath variation of MSNA with elevated tidal breathing. These findings indicate that during normal levels of tidal breathing most of the respiratory phase influence on muscle sympathetic outflow observed in normal conscious humans is independent of baroreceptor-sensed fluctuations in intrathoracic or intravascular pressures and of lung inflation-stimulated vagal afferent activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Sympathetic activation is associated with increases in EMG during fatiguing exercise.

The purpose of this study was to test the hypothesis that efferent sympathetic neural discharge is coupled with the development of muscle fatigue during voluntary exercise in humans. In 12 healthy subjects (aged 20-34 yr) we measured heart rate (HR), arterial blood pressure (AP), and noncontracting, skeletal muscle sympathetic nerve activity (MSNA) in the leg (peroneal nerve) before (control) and during each of three trials of submaximal (30% of maximum) isometric handgrip exercise performed to exhaustion. In six of the subjects of eletromyographic (EMG) activity of the exercising forearm was also measured. HR and AP increased significantly (P less than 0.05) in the 1st min of exercise in all trials. In contrast, neither MSNA nor EMG activity increased significantly above control during the 1st min of exercise, but both parameters subsequently increased in a progressive and parallel manner (P less than 0.05). The overall correlation coefficient between MSNA and EMG activity (144 observations) was 0.85 (P less than 0.001). With successive trials the magnitudes of the increases in HR, AP, MSNA, and EMG activity were greater at any absolute point in time during exercise. These results indicate that sympathetic activation to noncontracting skeletal muscle is directly related to the development of muscle fatigue (as assessed by the change in EMG) during prolonged isometric exercise in humans. Furthermore, our findings demonstrate that previous fatiguing contractions alter the time course of the sympathetic neural adjustments to exercise.

Central, femoral, and brachial circulation during exercise in hypoxia.

Central, femoral, and brachial circulation during exercise in hypoxia.